Under normal conditions, the human heart derives more than 60% of its energy from the oxidative metabolism of long chain fatty acids. In the ischaemic myocardium, however, oxidative metabolism of free fatty acids is suppressed, and anaerobic glucose metabolism predominates. Metabolic imaging can therefore provide useful information in the diagnosis and monitoring of various forms of heart disease.
Fatty acids have been radiolabelled with 11C and 18F for PET imaging, and 123I and 99mTc for SPECT radiopharmaceutical imaging [Eckelman et al, J. Nucl. Cardiol., 14, S100-S109 (2007)]. Eckelman et al stress that radiolabelling with an isotope other than 11C is in fact labelling a fatty acid analogue, and that care is needed that the substituent does not affect the ability of the analogue to trace important steps of the metabolic pathway.
Taki et al [Eur. J. Nucl. Med. Mol. Imaging, 34, S34-S48 (2007)] point out that early radioiodinated fatty acid analogues based on iodo-alkyl substituents were found to suffer significant in vivo metabolic deioidination. Radioiodinated fatty acid analogues incorporating iodo-phenyl moieties such as 123I-BMIPP and 123I-IPPA have, however, become established agents for such metabolic imaging (Taki et al, cited above):
                where I*=123I.        
The applications of “click chemistry” in biomedical research, including radiochemistry, have been reviewed by Nwe et al [Cancer Biother. Radiopharm., 24(3), 289-302 (2009)]. As noted therein, the main interest has been in the PET radioisotope 18F (and to a lesser extent 11C), plus “click to chelate” approaches for radiometals suitable for SPECT imaging such as 99mTc or 111In. 18F click-labelling of targeting peptides, giving products incorporating an 18F-fluoroalkyl-substituted triazole have been reported by Li et al [Bioconj. Chem., 18(6), 1987-1994 (2007)], and Hausner et al [J. Med. Chem., 51(19), 5901-5904 (2008)].
WO 2006/067376 discloses a method for labelling a vector comprising reaction of a compound of formula (I) with a compound of formula (II):

a compound of formula (III) with a compound of formula (IV)

in the presence of a Cu(I) catalyst, to give a conjugate of formula (V) or (VI) respectively:

wherein L1, L2, L3, and L4 are each Linker groups;                R* is a reporter moiety which comprises a radionuclide.        
R* of WO 2006/067376 is a reporter moiety which comprises a radionuclide for example a positron-emitting radionuclide. Suitable positron-emitting radionuclides for this purpose are said to include 11C, 18F, 75Br, 76Br, 124I, 82Rb, 68Ga, 64Cu and 62Cu, of which 11C and 18F are preferred. Other useful radionuclides are stated to include 123I, 125I, 131I, 211At, 99mTc, and 111In.
WO 2007/148089 discloses a method for radiolabelling a vector comprising reaction of a compound of formula (I) with a compound of formula (II):

or, a compound of formula (III) with a compound of formula (IV):

in the presence of a Cu(I) catalyst to give a conjugate of formula (V) or (VI) respectively:

wherein:                L1, L2, L3, and L4 are each Linker groups;        R* is a reporter moiety which comprises a radionuclide.        
In both WO 2006/067376 and WO 2007/148089, metallic radionuclides are stated to be suitably incorporated into a chelating agent, for example by direct incorporation by methods known to the person skilled in the art.
WO 2006/116629 (Siemens Medical Solutions USA, Inc.) discloses a method of preparation of a radiolabelled ligand or substrate having affinity for a target biomacromolecule, the method comprising:                (a) reacting a first compound comprising                    (i) a first molecular structure;            (ii) a leaving group;            (iii) a first functional group capable of participating in a click chemistry reaction; and optionally,            (iv) a linker between the first functional group and the molecular structure, with a radioactive reagent under conditions sufficient to displace the leaving group with a radioactive component of the radioactive reagent to form a first radioactive compound;                        (b) providing a second compound comprising                    (i) a second molecular structure;            (ii) a second complementary functional group capable of participating in a click chemistry reaction with the first functional group, wherein the second compound optionally comprises a linker between the second compound and the second functional group;                        (c) reacting the first functional group of the first radioactive compound with the complementary functional group of the second compound via a click chemistry reaction to form the radioactive ligand or substrate; and        (d) isolating the radioactive ligand or substrate.        
WO 2006/116629 teaches that the method therein is suitable for use with the radioisotopes: 124I, 18F, 11C, 13N and 15O with preferred radioisotopes being: 18F, 11C, 123I, 124I, 127I, 131I, 76Br, 64Cu, 99mTC, 90Y, 67Ga, 51Cr, 192Ir, 99Mo, 153Sm and 201Tl. WO 2006/116629 teaches that other radioisotopes that may be employed include: 72As, 74As, 75Br, 55Co, 61Cu, 67Cu, 68Ga, 68Ge, 125I, 132I, 111In, 52Mn, 203Pb and 97Ru. WO 2006/116629 does not, however, provide any specific teaching on how to apply the method to the radioiodination of biological molecules.
WO 2010/129572 describes PET radiotracers for imaging fatty acid metabolism and storage having one of the following formulae:
                where: n is 10-24, m is 1-10 and X is a halogen.        
WO 2010/129572 teaches that at least one atom of the above chemical structures can be a radionuclide, preferably a positron-emitting radioisotope. 18F is the main radioisotope described. The structures shown would not be expected to be suitable for labelling with radioiodine, since if X were to be iodine that requires an iodoalkyl group, and such groups are known to be unstable with respect to deiodination in vivo.
Kim et al [Bioconj. Chem., 20(6), 1139-1145 (2009) disclose 18F-labelled fatty acid analogues for PET imaging of myocardial metabolism:

The 18F-fatty acids were prepared via click cycloaddition, wherein an 18F-alkyne was coupled to an azido-fatty acid, to generate the triazole ring.
PET imaging with 18F typically requires the availability of a cyclotron facility on the same site as the hospital, since 18F has a short half-life (110 minutes) and the desired radiotracer needs to be synthesised. The availability of cameras suitable for PET imaging is consequently much less widespread than SPECT cameras. There is therefore still a need for alternative radioiodinated fatty acids suitable for more routine clinical imaging, especially using SPECT radiopharmaceutical imaging.
The longer half-life of 123I compared to 18F enables the cyclotron for its production to be up to one day's transport time from the end user. This makes it possible for a single cyclotron to be able to supply a continent rather than a city, as is the case with 18F fluorine production.